Clinical Findings and Genetic Expression Profiling of Three Pigmented Lesions of the Optic Nerve

Alba, Manuel A. de; Villegas, Víctor M.; Gold, Aaron S.; Wildner, Andrea; Ehlies, Fiona J.; Latiff, Azeema; Murray, Timothy G.

doi:10.1155/2015/590659

Cited by 9 publications

(21 citation statements)

References 21 publications

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“…For instance, genetic similarities to uveal melanoma have been reported in a case of a leptomeningeal melanocytoma [21]. Melanocytomas of the optic nerve have been reported to show a class 1A genetic signature [22]. However, blue nevi – in contrast to other skin and conjunctival melanocytic lesions arising from epithelial melanocytes (typical nevus and melanoma) – have GNAQ mutations which are similar to those found in uveal melanoma [19, 23].…”

Section: Discussionmentioning

confidence: 99%

Melanocytoma of the Conjunctiva: Clinicopathologic Features of Three Cases

2019

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Background: Melanocytoma (magnocellular nevus) is a jet-black benign lesion histologically composed of polygonal tumor cells with small, inconspicuous nuclei and abundant cytoplasm. Melanocytomas in general are rare. Most cases occur in the optic nerve head. Conjunctival melanocytoma (magnocellular nevus) is extremely rare, and only 3 lesions of the ocular surface have been reported. Objectives: To describe the clinical and histological spectrum of conjunctival melanocytoma and discuss differential diagnoses of this rare lesion. Method: Four heavily pigmented conjunctival lesions were excised for slight tumor growth and histologically processed. The specimens were routinely stained with hematoxylin and eosin and periodic acid-Schiff. Sections were bleached and immunohistochemical stains were performed for CD68, HMB-45, S100, melanin, and Ki-67. Results: Histological examination revealed findings of a conjunctival melanocytoma in 3 cases. The fourth case was diagnosed histologically as a combined melanocytic lesion with a compound nevus and an inverted type A nevus. None of the lesions exhibited transition towards malignancy. The differential diagnoses included conjunctival melanoma, granular cell nevus, compound nevus with reactive changes, and blue nevus. Conclusions: Conjunctival melanocytic lesions suspicious for melanocytoma should be bleached to evaluate their cytologic features. CD68 can be helpful in identifying heavily pigmented melanomacrophages which may mimic a melanocytoma. As conjunctival melanocytomas are extremely rare, their pathogenesis may be different from that of other conjunctival nevi.

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Section: Discussionmentioning

confidence: 99%

Melanocytoma of the Conjunctiva: Clinicopathologic Features of Three Cases

2019

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“…Further work has shown that the class 1 profile is indicative of a differentiated melanocytic phenotype that is seen not only in low grade uveal melanomas, but also in benign uveal nevi, melanocytom as and even normal choroidal melanocytes. 22,23 In contrast, tumors with the class 2 profile exhibit features of cytologic de-differentiation and expression of cancer stem cell markers. 22,24 A large prospective multi-center clinical trial performed by the Collaborative Ocular Oncology Group (COOG) validated the prognostic accuracy of the 15-gene clinical-grade profile, and confirmed its superior prognostic accuracy compared to clinical, histopathologic, and chromosomal features.…”

Section: Introductionmentioning

confidence: 99%

Are Risk Factors for Growth of Choroidal Nevi Associated With Malignant Transformation? Assessment With a Validated Genomic Biomarker

Harbour

Paez-Escamilla

Cai

et al. 2019

American Journal of Ophthalmology

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Purpose: To test the hypothesis that widely used clinical risk factors for growth of choroidal nevi are associated with malignant transformation. Methods: Fine needle biopsy for assignment of gene expression profile (class 1 or class 2) was performed in 207 choroidal melanocytic tumors <3.5 mm in thickness. The class 2 profile was employed as a validated biomarker for malignant transformation. The following data were collected: patient age and sex, tumor diameter and thickness, distance of posterior tumor margin from the optic disc, and the presence or absence of serous retinal detachment, orange lipofuscin pigment, drusen, retinal pigment epithelial fibrosis, retinal pigment epithelial atrophy, visual symptoms, and documented tumor growth. Results: Clinical features associated with the class 2 profile included patient age >60 years and tumor thickness >2.25 mm (Fisher exact test, P=.002 for both). Documented growth was not associated with the class 2 profile (P=.5). The odds ratio of a tumor having the class 2 profile was 2.8 (95% confidence interval, 1.3–5.9) for patient age >60 years old and 3.5 (95% confidence interval, 1.4–8.8) for tumor thickness >2.25 mm. For patients with both risk factors, the “number needed to treat” to identify one patient with a class 2 tumor was 4.3 (P=.0002). No other clinical feature or combination of features was associated with the class 2 profile. Conclusions: None of the widely used choroidal nevus risk factors for tumor growth, nor documented growth itself, is pathognomonic of malignant transformation as defined by class 2 gene expression profile. Patient age and tumor thickness may be helpful for identifying small choroidal melanocytic tumors that are more likely to have the class 2 profile. Observation for growth prior to treatment continues to be reasonable for most patients with suspicious choroidal nevi.

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“…[1][2][3][4] Recently, karyotype analysis, comparative genomic hybridization, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, mutational profiling, and gene-expression profiling (GEP) by incisional biopsy or fine-needle aspiration biopsy (FNAB) have elucidated the most common genetic mutations associated with uveal melanoma and have become important tools for prognostication. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] Castle Biosciences (Tucson, AZ) has developed a commercially available assay (DecisionDx-UM) to routinely provide patients with uveal melanoma prognostic information about their tumors. 13 The assay has been validated in a multicenter prospective clinical trial in the Collaborative Ocular Oncology Group Report Number 1, where it correctly classified tumors in 97.2% of cases.…”

Section: Introductionmentioning

confidence: 99%

“…14 Multiple surgical strategies have been described for FNAB. 9,[15][16][17][18][19][20][21] The transvitreal pars plana technique may be performed using a microscope or under indirect ophthalmoscopy, using standard vitrectomy techniques or directly with a 23-gauge (G)/25G/27G needle. [15][16][17][18]20,21 Treatment of the tumor may be performed before or after FNAB.…”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17][18]20,21 Treatment of the tumor may be performed before or after FNAB. 9 Risks associated with the transvitreal biopsy include vitreous hemorrhage, cataract, rhegmatogenous retinal detachment, and hypotony. [15][16][17][18]20,21 Transscleral biopsies may be performed under direct visualization, using magnifying loupes, or under the microscope.…”

Section: Introductionmentioning

confidence: 99%

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Fine-Needle Aspiration Biopsy for Molecular Genomic Classification: Evaluation of Transscleral vs Transvitreal Biopsy

Villegas

Gold²,

Murray³

2018

Journal of VitreoRetinal Diseases

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To evaluate the transvitreal and transscleral fine-needle aspiration biopsy (FNAB) approach for molecular classification with gene-expression profiling (GEP) of uveal melanoma. Methods: Institutional review board-approved single-surgeon retrospective analysis of a consecutive case series of all patients undergoing FNAB using a 25-gauge-needle multipass approach for GEP analysis of uveal melanoma between 2012 and 2016. All FNAB specimens were processed for uveal melanoma diagnostic testing using a standard processing approach, and all testing was completed at a single laboratory (Castle Biosciences, Inc.). Results: Three hundred fifty-three eyes (353 patients) were included. Transvitreal biopsies were performed in 216 eyes (216/ 353, 61.2%), whereas transscleral biopsies were performed in 137 eyes (137/353, 38.8%). Twenty biopsies exhibited multiple gene failure (20/353, 5.6%). Excessive fluid biopsy volume was the primary association with reported multiple gene failure, occurring in 10 of 20 eyes (50%). FNAB performed via the transvitreal approach was significantly more likely to have an excessive volume report compared with transscleral biopsy (18/216, 8.3% vs 1/137, 0.7%; P < .001). Conclusions: FNAB performed via a transscleral or transvitreal multipass approach utilizing a 25-gauge needle achieves molecular classification in 95% of all patients undergoing treatment for presumed uveal melanoma independent of tumor size. Complications related to FNAB using these techniques are rare and may be associated with the presentation of the uveal melanoma.

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Clinical Findings and Genetic Expression Profiling of Three Pigmented Lesions of the Optic Nerve

Cited by 9 publications

References 21 publications

Melanocytoma of the Conjunctiva: Clinicopathologic Features of Three Cases

Melanocytoma of the Conjunctiva: Clinicopathologic Features of Three Cases

Are Risk Factors for Growth of Choroidal Nevi Associated With Malignant Transformation? Assessment With a Validated Genomic Biomarker

Fine-Needle Aspiration Biopsy for Molecular Genomic Classification: Evaluation of Transscleral vs Transvitreal Biopsy

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